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Research ArticleNEUROPHARMACOLOGY

Regulation of Extracellular Concentrations of 5-Hydroxytryptamine (5-HT) in Mouse Striatum by 5-HT1A and 5-HT1B Receptors

Deborah A. Knobelman, Hank F. Kung and Irwin Lucki
Journal of Pharmacology and Experimental Therapeutics March 2000, 292 (3) 1111-1117;
Deborah A. Knobelman
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Hank F. Kung
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Irwin Lucki
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Abstract

The ability of selective serotonin (5-HT) receptor agonists to reduce the extracellular concentration of 5-HT was examined in the striatum of awake, unrestrained mice by in vivo microdialysis. Systemic administration of either 8-OH-PIPAT {R-(+)-trans-8-hydroxy-2-[N-n-propyl-N-(3′-iodo-2′-propenyl)] aminotetralin}, a novel 5-HT1A receptor agonist, or CP 94,253, a selective 5-HT1B receptor agonist, resulted in significant dose-related reductions of striatal 5-HT. The effect of 8-OH-PIPAT (1.0 mg/kg) was blocked by pretreatment with WAY 100635 (0.1 mg/kg), a selective 5-HT1A receptor antagonist, but it was not blocked by pretreatment with GR 127935 (0.056 mg/kg), a selective 5-HT1B/1D receptor antagonist. The effect of CP 94,253 (1.0 mg/kg) was blocked by pretreatment with GR 127935 (0.056 mg/kg) but was not blocked by pretreatment with WAY 100635 (0.1 mg/kg). Neither WAY 100635 nor GR 127935 altered extracellular 5-HT levels at the doses that were able to completely block the effects of either 8-OH-PIPAT or CP 94,253. The present findings suggest that, on systemic administration, both 8-OH-PIPAT and CP 94,253 are potent and selective agonists at the somatodendritic 5-HT1A autoreceptor and terminal 5-HT1B/1D autoreceptor, respectively, and are each able to cause decreases in extracellular levels of 5-HT in the mouse striatum by activating a distinct set of receptors.

Footnotes

  • Send reprint requests to: Dr. Irwin Lucki, University of Pennsylvania, Department of Psychiatry, 3600 Market St., Room 748, Philadelphia, PA 19104-2648. E-mail: lucki{at}pharm.med.upenn.edu

  • ↵1 This research was supported by U.S. Public Health Service Grant MH 48125 and predoctoral National Research Service Award Grant MH 12147 (to D.A.K.).

  • Abbreviations:
    5-HT
    serotonin
    8-OH-DPAT
    8-hydroxy-2-dipropylaminotetralin
    8-OH-PIPAT
    R-(+)-trans-8-hydroxy-2-[N-n-propyl-N-(3′-iodo-2′-propenyl)] aminotetralin
    AUC
    area under the curve
    TFMPP
    N-(3-trifluoromethylphenyl)piperazine
    • Received December 8, 1999.
    • Accepted December 8, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 292 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 292, Issue 3
1 Mar 2000
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Research ArticleNEUROPHARMACOLOGY

Regulation of Extracellular Concentrations of 5-Hydroxytryptamine (5-HT) in Mouse Striatum by 5-HT1A and 5-HT1B Receptors

Deborah A. Knobelman, Hank F. Kung and Irwin Lucki
Journal of Pharmacology and Experimental Therapeutics March 1, 2000, 292 (3) 1111-1117;

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Research ArticleNEUROPHARMACOLOGY

Regulation of Extracellular Concentrations of 5-Hydroxytryptamine (5-HT) in Mouse Striatum by 5-HT1A and 5-HT1B Receptors

Deborah A. Knobelman, Hank F. Kung and Irwin Lucki
Journal of Pharmacology and Experimental Therapeutics March 1, 2000, 292 (3) 1111-1117;
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